In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multina

The distinct relation between trait impulsivity and cortical morphometry in CU and HC might underlie inefficient control over behavior resulting in maladaptive impulsive behaviour such as cocaine abuse.

Diffusion tensor imaging studies have provided evidence for white matter (WM) alterations in cocaine users. While polysubstance use is a widespread phenomenon among cocaine users, its role in WM alterations in cocaine users is currently unknown. This study examined the relation between the number of substances that are used(cocaine, alcohol and marijuana) and WM alterations in 67 male non-drug users and 67 male regular cocaine users, who were classified into five groups based on the number of used substances. Diffusion-weighted images were acquired on a 3.0 T magnetic resonance imaging scanner. Using tract-based spatial statistics we demonstrated that there was a negative relation between the number of used substances and fractional anisotropy, a global measure of WM integrity. Also, we demonstrated a positive relation between the number of used substance and radial diffusivity within the prefrontal lobe, suggesting an increase in demyelination with the number of used substances. We did not find a dose-effect between the level of substance use and WM alterations. The results of the current study may reflect the presence of a pre-existing vulnerability to polysubstance use resulting from prefrontal WM abnormalities and related impaired cognitive control although WM alterations because of polysubstance use cannot be fully excluded. This study is an important first step in understanding the problems related to polysubstance use among cocaine users.

Background and aimsChildhood trauma is associated with increased levels of anxiety later in life, an increased risk for the development of substance use disorders, and neurodevelopmental abnormalities in the amygdala and frontostriatal circuitry. The aim of this study was to investigate the (neurobiological) link among childhood trauma, state anxiety, and amygdala-frontostriatal activity in response to cocaine cues in regular cocaine users.MethodsIn this study, we included 59 non-treatment seeking regular cocaine users and 58 non-drug using controls. Blood oxygenation level-dependent responses were measured using functional magnetic resonance imaging while subjects performed a cue reactivity paradigm with cocaine and neutral cues. Psychophysiological interaction analyses were applied to assess functional connectivity between the amygdala and other regions in the brain. Self-report questionnaires were used to measure childhood trauma, state anxiety, drug use, drug use severity, and craving.ResultsNeural activation was increased during the presentation of cocaine cues, in a widespread network including the frontostriatal circuit and amygdala in cocaine users but not in controls. Functional coupling between the amygdala and medial prefrontal cortex was reduced in response to cocaine cues, in both cocaine users and controls, which was further diminished with increasing state anxiety. Importantly, amygdala-striatal connectivity was positively associated with childhood trauma in regular cocaine users, while there was a negative association in controls. At the behavioral level, state anxiety was positively associated with cocaine use severity and craving related to negative reinforcement.ConclusionChildhood trauma is associated with enhanced amygdala-striatal connectivity during cocaine cue reactivity in regular cocaine users, which may contribute to increased habit behavior and poorer cognitive control. While we cannot draw conclusions on causality, this study provides novel information on how childhood trauma may contribute to the development and persistence of cocaine use disorder.

These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity.

Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.